Erratum: FAS-ligand regulates differential activation-induced cell death of human T-helper 1 and 17 cells in healthy donors and multiple sclerosis patients

Cencioni, Maria Teresa; Santini, Simonetta; Ruocco, Gabriella; Borsellino, Giovanna; Bardi, Marco De; Grasso, Maria Grazia; Ruggieri, Serena; Gasperini, Claudio; Centonze, Diego; Barilá, Daniela; Battistini, Luca; Volpe, Elisabetta

doi:10.1038/cddis.2015.164

Cited by 10 publications

(9 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, differential cell death sensitivity between Th1 and Th17 cells is also confirmed in cells derived from MS patients ( 100 ). Since the homeostatic regulation of cell expansion by cell death is similar in HD and MS patients, the persistence of Th17 cells in MS disease may be due to altered mechanisms of Th17 cell generation in MS patients compared to HD.…”

Section: Fas–fasl Pathway In T Cells With Pathogenic Role In Msmentioning

confidence: 84%

“…Several studies have demonstrated that murine Th17 cells are more resistant to AICD than another Th subset called Th1, characterized by predominant and abundant interferon (IFN)-γ production ( 98 – 100 ). Th1 cells have a pathogenic role in MS ( 101 ), particularly in the initiation of the inflammatory response, through the activation of macrophages ( 102 ) and the induction of increased vascular adherence that facilitates access in the CNS of the critical effector cells sustaining tissue damage, such as Th17 cells ( 103 ).…”

Section: Fas–fasl Pathway In T Cells With Pathogenic Role In Msmentioning

confidence: 99%

“…Interestingly, low FasL and FLIP expression in Th17 cells compared to Th1 cells are the major mechanisms regulating their differential cell death sensitivity ( 98 – 100 ) (Figure 2 ). Recently, it has been demonstrated that low levels of mitogen-activated protein kinases (MAPKs), such as Erk1/2 and p38α, upon TCR stimulation, alter FasL expression and AICD sensitivity of Th17 cells ( 106 ).…”

Section: Fas–fasl Pathway In T Cells With Pathogenic Role In Msmentioning

confidence: 99%

See 2 more Smart Citations

Fas–Fas Ligand: Checkpoint of T Cell Functions in Multiple Sclerosis

et al. 2016

View full text Add to dashboard Cite

Fas and Fas Ligand (FasL) are two molecules involved in the regulation of cell death. Their interaction leads to apoptosis of thymocytes that fail to rearrange correctly their T cell receptor (TCR) genes and of those that recognize self-antigens, a process called negative selection; moreover, Fas–FasL interaction leads to activation-induced cell death, a form of apoptosis induced by repeated TCR stimulation, responsible for the peripheral deletion of activated T cells. Both control mechanisms are particularly relevant in the context of autoimmune diseases, such as multiple sclerosis (MS), where T cells exert an immune response against self-antigens. This concept is well demonstrated by the development of autoimmune diseases in mice and humans with defects in Fas or FasL. In recent years, several new aspects of T cell functions in MS have been elucidated, such as the pathogenic role of T helper (Th) 17 cells and the protective role of T regulatory (Treg) cells. Thus, in this review, we summarize the role of the Fas–FasL pathway, with particular focus on its involvement in MS. We then discuss recent advances concerning the role of Fas–FasL in regulating Th17 and Treg cells’ functions, in the context of MS.

show abstract

Section: Fas–fasl Pathway In T Cells With Pathogenic Role In Msmentioning

confidence: 84%

Section: Fas–fasl Pathway In T Cells With Pathogenic Role In Msmentioning

confidence: 99%

Section: Fas–fasl Pathway In T Cells With Pathogenic Role In Msmentioning

confidence: 99%

See 1 more Smart Citation

Fas–Fas Ligand: Checkpoint of T Cell Functions in Multiple Sclerosis

et al. 2016

View full text Add to dashboard Cite

show abstract

“…We posit that other T cell subsets might manipulate SAP-SLAM receptor signaling to elude RICD (e.g. Th17 cells [36]) or adjust RICD sensitivity at distinct phases of the effector T cell response. For example, effector cells that progress into long-lived memory T cell pools could be shaped in part by SAP-SLAM receptor signaling alterations that promote their persistence.…”

Section: Discussionmentioning

confidence: 99%

FOXP3 renders activated human regulatory T cells resistant to restimulation-induced cell death by suppressing SAP expression

Katz

Voss

Yan

et al. 2018

Cellular Immunology

View full text Add to dashboard Cite

Restimulation-induced cell death (RICD) is an apoptotic program that regulates effector T cell expansion, triggered by repeated stimulation through the T cell receptor (TCR) in the presence of interleukin-2 (IL-2). Although CD4 regulatory T cells (Tregs) consume IL-2 and experience frequent TCR stimulation, they are highly resistant to RICD. Resistance in Tregs is dependent on the forkhead box P3 (FOXP3) transcription factor, although the mechanism remains unclear. T cells from patients with X-linked lymphoproliferative disease (XLP-1), that lack the adaptor molecule SLAM-associated protein (SAP), are also resistant to RICD. Here we demonstrate that normal Tregs express very low levels of SAP compared to conventional T cells. FOXP3 reduces SAP expression by directly binding to and repressing the SH2D1A (SAP) promoter. Indeed, ectopic SAP expression restores RICD sensitivity in human FOXP3 Tregs. Our findings illuminate the mechanism behind FOXP3-mediated RICD resistance in Tregs, providing new insight into their long-term persistence.

show abstract

“…Currently, the survival period of activated Th17 cells remains controversial ( 35 , 36 ). In this study, we found that Perp −/− Th17 cells were resistant to apoptosis induced by chronic TCR stimulation and anti-Fas, and increased frequency of peripheral blood Th17 cells was detected in EAE Lck-Cre × Perp fl/fl mice.…”

Section: Discussionmentioning

confidence: 99%

Loss of Perp in T Cells Promotes Resistance to Apoptosis of T Helper 17 Cells and Exacerbates the Development of Experimental Autoimmune Encephalomyelitis in Mice

Zhou

Leng

et al. 2018

Front. Immunol.

View full text Add to dashboard Cite

T helper 17 (Th17) cells are crucial for the pathogenesis of multiple sclerosis (MS) in humans and experimental autoimmune encephalomyelitis (EAE) in animals. High frequency of Th17 cells and low sensitivity to activation-induced cell death (AICD) are detected in MS patients. However, the mechanisms underlying apoptosis resistance of T cells remain unclear. Perp is an apoptosis-associated target of p53 and implicated in the development of cancers. Here, we show that loss of Perp in T cells does not affect Th1, Th17, or Treg cell differentiation, but does significantly increase the resistance of Perp−/− Th17 cells to AICD and anti-Fas in Lck-Cre × Perpfl/fl mice by inhibiting the caspase-dependent apoptotic pathway. Moreover, Lck-Cre × Perpfl/fl mice exhibited earlier onset of EAE and severe spinal cord inflammation and demyelination, accompanied by increased levels of pro-inflammatory cytokines and enlarged population of Th17 cells. Therefore, Perp deletion promoted Th17 responses and exacerbated the development and severity of EAE.

show abstract

Erratum: FAS-ligand regulates differential activation-induced cell death of human T-helper 1 and 17 cells in healthy donors and multiple sclerosis patients

Cited by 10 publications

References 0 publications

Fas–Fas Ligand: Checkpoint of T Cell Functions in Multiple Sclerosis

Fas–Fas Ligand: Checkpoint of T Cell Functions in Multiple Sclerosis

FOXP3 renders activated human regulatory T cells resistant to restimulation-induced cell death by suppressing SAP expression

Loss of Perp in T Cells Promotes Resistance to Apoptosis of T Helper 17 Cells and Exacerbates the Development of Experimental Autoimmune Encephalomyelitis in Mice

Contact Info

Product

Resources

About